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Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy

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ClinicalTrials.gov Identifier: NCT01852162
Recruitment Status : Completed
First Posted : May 13, 2013
Results First Posted : March 17, 2015
Last Update Posted : March 17, 2015
Sponsor:
Information provided by (Responsible Party):
University of Florida

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Coronary Artery Disease
Interventions Drug: Dabigatran
Drug: Placebo
Enrollment 35
Recruitment Details This was a prospective, randomized, double-blind, placebo-controlled PD study conducted in patients with CAD on maintenance DAPT with aspirin and clopidogrel. Patients were screened at the Division of Cardiology of the University Of Florida College Of Medicine - Jacksonville from February 2012 to December 2013.
Pre-assignment Details  
Arm/Group Title Dabigatran Placebo
Hide Arm/Group Description Patients randomized to the dabigatran arm received dabigatran 150mg twice/daily for 7 (±3) days. Patients randomized to the placebo arm received matching placebo tablets twice/daily for 7 (±3) days.
Period Title: Overall Study
Started 18 17
Completed 14 16
Not Completed 4 1
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             3             1
Arm/Group Title Dabigatran Placebo Total
Hide Arm/Group Description Dabigatran 150mg tablets Placebo tablets Total of all reporting groups
Overall Number of Baseline Participants 14 16 30
Hide Baseline Analysis Population Description
Patients were considered for analysis of the PD end points if they completed both visits and had a compliance >80% to study drug, clopidogrel and aspirin. All patients who received any dose of study medication were considered for analysis of safety and any other adverse events.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 16 participants 30 participants
65  (8) 59  (9) 63  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
Female
3
  21.4%
3
  18.8%
6
  20.0%
Male
11
  78.6%
13
  81.3%
24
  80.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   6.3%
1
   3.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
  28.6%
4
  25.0%
8
  26.7%
White
10
  71.4%
11
  68.8%
21
  70.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 14 participants 16 participants 30 participants
14 16 30
1.Primary Outcome
Title TRAP-induced Platelet Aggregation
Hide Description TRAP-induced platelet aggregation measured by light transmittance aggregometry (LTA) was similar between groups
Time Frame 1 week
Hide Outcome Measure Data
Hide Analysis Population Description
TRAP-induced platelet aggregation
Arm/Group Title Dabigatran Placebo
Hide Arm/Group Description:
Dabigatran 150mg
Placebo tablets
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: percentage of aggregation
74  (8) 77  (6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran, Placebo
Comments Assuming a 20% relative difference in TRAP induced MPA between dabigatran and placebo with a common standard deviation of 10%, 13 patients with available data needed to be randomized to obtain a 95% power and 2-sided alpha=0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments An analysis of covariance (ANCOVA) method with a general linear model, using the corresponding baseline PD value as a covariate, was used to evaluate the comparisons between dabigatran and placebo at 7 days.
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Platelet Reactivity Measured by LTA
Hide Description Multiple measures of platelet reactivity evaluating purinergic and non-purinergic signaling pathways were assessed by light transmittance aggregometry (LTA).
Time Frame 1-week
Hide Outcome Measure Data
Hide Analysis Population Description
Platelet aggregation measured by LTA
Arm/Group Title Dabigatran Placebo
Hide Arm/Group Description:
Dabigatran 150mg
Placebo tablets
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: percentage of aggregation
ADP-induced platelet aggregation 49.5  (16.6) 44.6  (15.0)
Arachidonic acid-induced platelet aggregation 6.9  (18.2) 6.0  (1.5)
Collagen-induced platelet aggregation 42.6  (22.8) 34.9  (22.0)
3.Secondary Outcome
Title Platelet Reactivity Measured by Multiple Electrode Aggregometry.
Hide Description Multiple measures of platelet reactivity evaluating purinergic and non-purinergic signaling pathways were assessed by multiple electrode aggregometry.
Time Frame 1-week
Hide Outcome Measure Data
Hide Analysis Population Description
Platelet aggregation measured by multiple electrode aggregometry.
Arm/Group Title Dabigatran Placebo
Hide Arm/Group Description:
Dabigatran 150mg
Placebo tablets
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: arbitrary aggregation units
TRAP-induced platelet aggregation 1176.4  (274) 1210.6  (275)
ADP-induced platelet aggregation 482.2  (199) 454.0  (227)
Arachidonic acid-induced platelet aggregation 238.9  (88) 230.1  (115)
Collagen-induced platelet aggregation 559.4  (180) 532.5  (182)
4.Secondary Outcome
Title Clot Kinetic: Thrombin Activity
Hide Description Parameters related to thrombin activity and velocity of thrombus generation (reaction time: R; time to maximum rate of thrombus generation: TMRTG) were evaluated by thromboelastography.
Time Frame 1-week
Hide Outcome Measure Data
Hide Analysis Population Description
Clot kinetic assessed by citrated-kaolin thromboelastography
Arm/Group Title Dabigatran Placebo
Hide Arm/Group Description:
Dabigatran 150mg
Placebo tablets
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: minutes
R 12.25  (2.6) 6.76  (1.1)
TMRTG 14.32  (3) 8.4  (1.6)
5.Secondary Outcome
Title Clot Kinetic: Clot Stength
Hide Description Clot strength (maximal amplitude:MA) was assessed by thromboelastography.
Time Frame 1-week
Hide Outcome Measure Data
Hide Analysis Population Description
Clot kinetic assessed by citrated-kaolin thromboelastography
Arm/Group Title Dabigatran Placebo
Hide Arm/Group Description:
Dabigatran 150mg
Placebo tablets
Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: mm
63.7  (4.4) 62.9  (6.7)
Time Frame 7 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dabigatran Placebo
Hide Arm/Group Description Dabigatran 150mg tablets Placebo tablets
All-Cause Mortality
Dabigatran Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Dabigatran Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/18 (5.56%)      0/17 (0.00%)    
Cardiac disorders     
myocardial infarction  [1]  1/18 (5.56%)  1 0/17 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
One patient in the dabigatran group had a non-ST-segment elevation myocardial infarction during study treatment, which was medically managed and required study drug discontinuation
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Dabigatran Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      0/17 (0.00%)    
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dominick Angiolillo, MD, PhD
Organization: University of Florida
Phone: 904-244-3933
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01852162     History of Changes
Other Study ID Numbers: UFJ 2011-112
First Submitted: May 8, 2013
First Posted: May 13, 2013
Results First Submitted: February 3, 2015
Results First Posted: March 17, 2015
Last Update Posted: March 17, 2015